DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?

Harju, TeklaUniv Oulu, Res Unit Clin Med, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland. (författare)

DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia : is there a causal relationship?

Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients.

Hurme-Niiranen, AnriUniv Oulu, Res Unit Clin Med, Oulu, Finland.;Univ Oulu, Med Res Ctr, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland. (författare)
Suo-Palosaari, MariaOulu Univ Hosp, Dept Diagnost Radiol, Oulu, Finland.;Oulu Univ Hosp, Res Unit Hlth Sci & Technol, Oulu, Finland.;Univ Oulu, Oulu, Finland. (författare)
Nielsen, Stine NygaardCopenhagen Univ Hosp, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark. (författare)
Hinttala, ReettaUniv Oulu, Res Unit Clin Med, Oulu, Finland.;Univ Oulu, Med Res Ctr, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland. (författare)
Schmiegelow, KjeldCopenhagen Univ Hosp, Rigshosp, Pediat Oncol Lab, Copenhagen, Denmark. (författare)
Uusimaa, JohannaUniv Oulu, Res Unit Clin Med, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.;Univ Oulu, Med Res Ctr, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland. (författare)
Harila-Saari, Arja H.Uppsala universitet,Barnonkologisk och neurologisk forskning(Swepub:uu)arjha456 (författare)
Niinimäki, RiittaUniv Oulu, Res Unit Clin Med, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland. (författare)
Univ Oulu, Res Unit Clin Med, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.Univ Oulu, Res Unit Clin Med, Oulu, Finland.;Univ Oulu, Med Res Ctr, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland. (creator_code:org_t)

Ingår i:The Pharmacogenomics Journal: Springer Nature23, s. 105-1111470-269X1473-1150

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